Sympathetic innervation of pulmonary circulation and its role in hypoxic pulmonary vasoconstriction

The purposes of this study were to localize the position of spinal center of sympathetic nerve which controls the pulmonary circulation, and to evaluate the role of pulmonary sympathetic nerve in hypoxic pulmonary vasoconstriction (HPV) in pithed rat model. The sympathetic preganglionic fibers arising from C₇–T₁₀ segments were stimulated electrically in succession. During stimulation the pulmonary vascular resistance (PVR) was increased in all segments tested, most significantly in C₇-T₄ (about 28 % above control value), obviously higher than that in T₅-T₁₀. The higher the stimulated spinal segments, the larger the ratio of ΔPVR/ΔSVR. Alveolar hypoxia (12%O₂–88% N₂) could induce HPV in pithed rat. In the presence of hypoxia, stimulation of T₁–T₃ segments caused a double increment in PVR and -P_p, as compared with those during normoxia (P<0.05). The data show that 1) the spinal center of sympathetic nerve regulating the vasomotion of pulmonary circulation is located in the C₇-T₄ segments; 2) the excitation of sympathetic nervous system during hypoxia could enhance HPV.     

Der Einfluß des Rauchens auf die hypoxische pulmonale Vasokonstriktion in der isolierten Lunge der Ratte — die Rolle der Prostaglandine und Leukotriene

Isolated rat lungs perfused with blood were used to determine the effects of cigarette smoke, delivered into the lung by a ventilator, on the pulmonary vascular resistance (PVR), and on the hypoxic pulmonary vasoconstriction (HPV), and to explore the role the prostsglandines (PG) and leukotrienes (LT) play in. that effect. The results showed that PVR did not change, while HPV was significantly enhanced by smoking. Indomethacin, an inhibitor of PG biosynthesis, administered in the perfusing blood (20 μg/ml) increased HPV in non-smoking lungs, but not in lungs after smoking. Diethylcarbamazine citrate (DEC, l mg/ml),an inhibitor of LT biosynthesis, decreased HPV before and after smoking. After perfusion with both indomethacin and DEC, HPV also decreased. It is suggested that LT act as mediators whereas PG as modulators in HPV, and PG and LT might play an important role in the increase of HPV by cigarette smoking.     

Effect of cigarette smoking on hypoxic pulmonary vasoconstriction and its relation to animal species and period of smoking

Summary The alteration in hypoxic pulmonary vasoconstriction (HPV) induced by cigarette smoking was studied in Wistar rats, piglets and in humans. The percentage change of pulmonary vascular resistance (δPVR%) and the amplitude of the systolic wave in impedance pneumorheogram (δH%) were used to estimate the strength of HPV. It was observed that immediately after acute cigarette smoking, HPV in rats increased (δPVR% from 55,0 ±15.6% to 102.3 ±12.4%), which is mainly mediated by leukotrienes (LTs); whereas HPV in piglets decreased (δPVR% from 65.2 + 12.5% to 55.9 ±9.8%), which is mainly mediated by β-adrenergic receptors, and HPV in humans also increased (δH% from 20.6±2.6% to 31.1 ±4.1%), in which prostaglandins and leukotrienes may play the role of mediators. However, after one-month cigarette smoking, the HPV in rats fell significantly (δPVR% 11.4±1.6%). An increase in synthesis of vasodilative prostaglandins and a decrease in leukotrienes synthesis may be the contributing factors to this alteration in HPV.     

ROLE OF f3-RECEPTOR IN THE RADIX ANGELICAE SINENSIS ATTENUATED HYPOXIC PULMONARY HYPERTENSJON IN RATS

Acute pulmonary hypertension was caused by inhalation of 5% 02 in rats. Pulmonary vascujar re- sistance (PVR) increased, but heart rate (HR), cardiac output (CO) and carotid arterial pressure (CAP) were not obviously changed. After an intravenous admini- stration of Radix Angelicae sinensis, the acute pulmonary hypertension induced by inhalation of 5% O2 could be attenuated, but this effect disappeared if propranolol was given before Radix Angelicae sinensis. In chronic experiments, the same results were obtained, but the protective effect of Radix Angelicae sinensis on heart function was not influenced by propranolol. It is suggested that Radix Angelicae sinensis rmght play a role by stimulating the βz-receptor in the prevention of acute and chronic hypoxic pulmonary hypertension. However, prevention of hypertrophy of the right ventricle and enhancement of heart function in chronic hypoxic rats might not be attributed to the β1 receptor in the heart.     

肺心营养合剂抑制吸烟引起的缺氧性肺血管收缩反应增强

20名健康男大学生 ,随机分为两组 ,分别服肺心营养合剂 (PX)和安慰剂 1个月 ,用肺阻抗血流图测定由吸烟引起的肺血管反应性的变化。结果表明 :吸烟可增强缺氧性肺血管收缩反应 (HPV) ,营养合剂则可抑制吸烟引起的 HPV增加。     

The regulating effects of protein kinase C on the tone of guinea-pig trachea and human lobus bronchi

Summary The regulating effects of protein kinase C (PKC) on the tone of guinea-pig trachea and human lobus bronchi were investigated by measuring the tone of isolated tracheal and bronchial strips. The effects of PKC on the tone of guinea-pig tracheal and human lobus bronchi were observed and compared. The results showed that: (1) PKC activator PMA induced concentration-dependent relaxation in guinea-pig isolated trachea strips. This relaxation was completely ablated by the pretreatment with 5 × 10^t-6mol/L Ro31-8220 which is a PKC-specific inhibitor, but was not affected by the removal of epithelium (EP), or by the pretreatment with propranolol (β-receptor blocker) or atropin (M-receptor blocker); (2) PMA led to concentration-dependent contraction in human lobus bronchi. This contractile response was completely depressed by the pretreatment with 5 × 10^t-6 mol/L Ro31-8220 and was partly inhibited by 1 × 10^t-5 mol/L isoptin (Ca²⁺-antagonist). but was not significantly affected by propranolol or atropin. It is concluded that PKC is involved in the regulation of airway smooth muscle tone. The regulating effects may vary in different animals.     

Effects of cigarette smoking on the function of metabolizing arachidonic acid and angiotensin I in the isolated perfused rat lungs

Summary The effects of acute and chronic cigarette smoking on the metabolism of exogenous arachidonic acid (AA) and angiotensin I (AI) in perfused isolated rat lungs were studied. The results showed that acute cigarette smoking did not alter the contents of 6-keto-PGF_1α (the stable metabolite of PGI₂) and TXB₂ (the stable metabolite of TXA₂) in the effluent and the increment of pulmonary artery pressure (†P_pa) caused by AA. The conversion of A I into A II was significantly increased (P<0.01), while the †P_{p a}, induced by A I injection was obviously decreased as compared with controls (P<0.05). After cigarette smoke exposure for 30 days, the †P_{p a} caused by AA or A I did, not differ from that of controls, but the contents of 6-ketoPGF_1α and A II increased more markedly than those in non-smoking rats,(P< 0.05). It is suggested that acute and chronic cigarette smoking in rats can promote the lung function of converting A I into A II, chronic smoking can increase the lung function of metabolizing AA into PGI₂.     

Effects of alpha adrenergic blockade during stellate ganglion stimulation on arrhythmias induced by acute myocardial ischemia in pigs

Summary The effects of α-adrenergic receptor blockade during stellate ganglion stimulation on arrhythmias induced by repeated coronary artery occlusion in pigs under spontaneous breathing were studied. Prazosin, α₁-receptor blocker, did not have any effect on the early ischemic dysrhythmia. Yohimbin, which selectively blocks α₂-receptor, significantly increased the number of premature ventricular complexes (19±3→ 32±2 PVC;P<0.01), but produced no effects on the percentage of appearance of ventricular fibrillation (VF) and ventricular tachycardia (VT). However, nonselective α-receptor blocker phentolamine significantly reduced the number of premature ventricular complexes (30.5 ± 4.5→ 11 ±3 PVC;P<0.05), but did not affect the frequency of occurrence of VF and VT. The above results show that α-adrenergic mechanisms do not play any important role in the genesis of arrhythmias during ischemia in the pig model.     

Relation of TXA2 and PGI2 to the difference in hypoxic pulmonary vasoconstriction between different strains of rats

TXB₂ and 6-keto-PGF₁ α levels in arterial and venous plasma of Wistar and Hilltop rats during hypoxia were measured to investigate the roles of TXA₂ and PGI₂ in hypoxic pulmonary vasoconstriction (HPV) and responsiveness difference of pulmonary vessels to hypoxia between different strains of rats. The results showed that PGI₂ might play an important role in maintaining the low resistance in pulmonary circulation of these two strains of rats. Increased TXA₂ during hypoxia may partially mediate HPV in Wistar rats, while augmented PGI₂ during hypoxia may modulate HPV in Wistar rats. This might be the important mechanism responsible for more intensive responsiveness of pulmonary vessels to hypoxia in Hilltop rats than in Wistar rats.     

支气管上皮源性因子在吸烟及缺氧所致肺血管反应中的作用

用滴注、生物检测系统观察支气管上皮产物对肺血管张力的作用及缺氧与吸烟对支气管上皮产物生成的影响。发现离体猪支气管上皮可分泌舒张因子（EpDRF），使肺动脉舒张，其作用不依赖于内皮。缺氧的支气管灌流液使缺氧性肺血管收缩反应（HPV）由31.7％降至─7.4％，说明EPDRF在HPV中起调节作用。通烟使猪肺动脉张力降低23％，支气管通烟时灌流液使肺动脉张力降低47.5％，为通烟和EpDRF作用之和。     

一氧化氮对急、慢性缺氧大鼠血流动力学及缺氧性肺血管收缩反应的影响

观察了吸入０．００４％的一氧化氮（ＮＯ）对急、慢性缺氧大鼠血流动力学、缺氧性肺血管收缩反应（ＨＰＶ）、血气及高铁血红蛋白（ＭｅｔＨｂ）的影响。结果表明：（１）常氧吸入ＮＯ时能明显降低慢性缺氧大鼠肺动脉平均压（Ｐｐａ）和肺血管阻力（ＰＶＲ），但对正常大鼠的Ｐｐａ和ＰＶＲ无明显影响；（２）慢性缺氧大鼠急性缺氧时ＨＰＶ较正常大鼠弱，吸入ＮＯ不但降低两者的急性缺氧肺动脉高压，且完全逆转两者的ＨＰＶ；（３）吸入ＮＯ对急、慢性缺氧大鼠体循环血流动力学、血气及ＭｅｔＨｂ含量无明显影响。提示吸入ＮＯ能选择性降低，急、慢性缺氧性肺动脉高血压，且逆转ＨＰＶ。     

Effects of prostaglandins and leukotrienes on hypoxic pulmonary vasoconstriction in rats

Alveolar hypoxia can induce pulmonary vaso-constriction,but the mechanism of hypoxic pul-monary vasoconstriction remains unknown. It mightrelate to arachidonic acid released from endotheliumor to the vasoactive substances released from othercells in lung tissue during hypoxia.Furthermore,theextra- pulmonary reflex and the directive effectof hy-poxia on pulmonary vascular smooth muscles mightalso be involved.In this study,we conducted in vivorats experiment and employed in vitro perfused lungex…     

Effects of cigarette smoking,hypoxia and vasoactive mediators on the production of PGI2 and TXA2 in cultured pulmonary artery endothelial cells

Summary Effects of cigarette smoke extract (CSE) and some vasoactive mediators on the production of PGI₂ and TXA₂ in normoxic and hypoxic pulmonary artery endothelial cells (PAECs) in culture were studied. The production of PGI₂ in PAECs was inhibited by hypoxia or verapamil, but promoted by angiotensin II (A II), noradrenaline (NE) or platelet activating factor (PAF), while that of TXA₂ slightly increased except when treated with PAF. The effect of A II, NE, PAF and verapamil, however, was not influenced by hypoxia. CSE inhibited the production of PGI₂ in normoxic PAECs but did not further reduce 6-keto-PGF_1α in hypoxic PAECs medium. The results suggested that a) the production of PGI₂ during hypoxia might be stimulated by vasoactive mediators produced during hypoxia, not by hypoxia directly; b) the production and release of PGI, were related to intracellular calcium, c) the augmented production of PGI₂ might be one of the mechanisms in the pulmonary vasodilating role of PAF: and d) prostaglandin production might be associated with the alteration of hypoxic pulmonary vasoreactivity after cigarette smoking.     

Effects of 3，4－Dihydroxyacetophenone （3，4－DHAP） on Hypoxic Pulmonary and Systemic Vascular Response in Dogs

（王迪浔）（明志）（余上斌）Ｅｆｆｅｃｔｓｏｆ３，４－Ｄｉｈｙｄｒｏｘｙａｃｅｔｏｐｈｅｎｏｎｅ（３，４－ＤＨＡＰ）ｏｎＨｙｐｏｘｉｃＰｕｌｍｏｎａｒｙａｎｄＳｙｓｔｅｍｉｃＶａｓｃｕｌａｒＲｅｓｐｏｎｓｅｉｎＤｏｇｓ￥ＦａｒｍａｎＵｌｌａｈ；ＷＡＮ...     

慢性束缚应激引起的胃粘膜细胞保护作用及其机制

研究慢性应激对乙醇灌胃所致胃粘膜损伤的影响并探讨其机制。方法：采用慢性束缚应激 （ｃｒｏｎｉｃ　 ｒｅｓｔｒａｉｎｔ　　ｓｔｒｅｓｓ,　ＣＲＳ）法,并用７０％乙醇灌胃造成大鼠胃粘膜损伤模型。结果：①ＣＲＳ可对抗７０％乙醇灌胃 所致大鼠胃粘膜损伤,其作用具有明显的时间依赖性;双侧膈下迷走神经切除对ＣＲＳ的保护作用无影响,而腹腔 交感神经切除则使保护作用丧失。②多巴胺或异丙肾上腺素可使交感神经切除后的ＣＲＳ保护作用得到部分恢 复。去甲肾上腺素无作用;在交感神经完整大鼠,心得安或氟哌啶醇可抑制ＣＲＳ的保护作用,使用酚妥拉明无 效。③ＣＲＳ能降低正常及交感神经切除后大鼠血清胃泌素水平,但生长抑素无明显变化;ＣＲＳ对胃液总量及总酸 排出量无明显影响,但能增加胃壁结合粘液分泌。结论：ＣＲＳ时交感神经系统的激活参与了大鼠胃粘膜适应性 细胞保护,且可能通过多巴胺和肾上腺素能β受体介导,胃壁结合粘液分泌增加可能是其保护胃粘膜机制之一。     

冠状动脉与周围动脉α肾上腺素受体亚型的异同

研究用12只β受体阻断的麻醉杂种犬,冠脉左旋支及左股动脉用腹主动脉血经恒压泵恒流灌注。交感神经电刺激(左星状神经节及腹腔交感链)与不同浓度去甲肾上腺素(NE)一次动脉注射引起动脉收缩反应。冠脉对大、小剂量的NE反应都不被α1受体阻断剂减弱,提示NE引起的冠脉反应主要是通过突触后α2受体,股动脉对小剂量NE的反应不被α1受体阻断减弱,但对大剂量NE的反应却因α1受体阻断而明显受抑制,提示股动脉对小剂量NE的收缩反应主要是通过α2受体,α1受体阻断剂还能明显阻断冠脉与股动脉对交感神经刺激的部分反应,但只有在α1与α2受体同时被阻断后,才能完全消除交感神经刺激引起的动脉收缩反应,提示突触后α2受体也受神经支配。     

Prophylactic Anti-inflammation Inhibits Cigarette Smoke-induced Emphysema in Guinea Pigs

Chronicobstructivepulmonarydisease (COPD )isoneoftheleadingcausesofdeathinthepopula tion[1] .Morethan 70 %casesofCOPDarecausedbycigarettesmokeinthiscountry[2 ] ,andemphysemaisthemostimportantsmoke inducedlesion .ThoughcessationofsmokingisasimpleandefficientwaytodeceleratethedevelopmentofCOPD[3] ,restrictionofsmokingisfarfromsatisfactionbecauseoftheongo ingtobaccoindustry ,directorindirectadvertisementofcigarettesmoking ,andthepursuingforfashionofsmokingespeciallyinyounggenerations.Alterna…     

Effects of microinjection of L-glutamate into locus coeruleus complex area on respiration

Summary The experiments were performed on 55 rabbits vagotomied, anesthetized with urethane and immobilized with flaxedil. Injection of L-glutamate (L-glu) into the locus coeruleus complex (Lc-Sc) area led to a marked increase in respiratory frequency (RF) and phrenic nerve discharge rate (phr. d) (16±3.5% and 6.5±2.5%;P<0.01 andP<0.05, respectively), a decrease in inspiratory and expiratory duration, and no obvious change in blood pressure (Bp) was observed. While prazosin (0.5 μg/μl), yohimbin (4 (μg/μl) and propranolol (2μg/μl) were preinjected into the nuclei tractus solitraii (NTS) respectively, the above-mentioned effects of L-glu on respiration was blocked. These results indicate that the excitation of neurons in the Lc-Sc can induce an increase in RF and phr d and the excitative effect of L-glu on RF was mediated by α₁,α₂ and β-receptors in the NTS, while the effect on phrd was mediated differently. This project was supported by grant no. 3870190 from the National Natural Sciences Foundation of China.     

良性运动应激降低大鼠慢性吸烟引起的气道高反应性

目的研究良性运动应激对慢性吸烟引起的大鼠气道高反应性的影响。方法复制大鼠慢性吸烟模型后，进行运动训练，测定大鼠气道反应性、血浆皮质醇浓度，行苏木精-伊红染色观察肺组织病理变化。结果①吸烟组的气道反应性明显高于正常对照组（P〈0．05），而吸烟运动组的气道反应性显著低于吸烟组（P〈0．01），且与正常对照组无明显差异；②吸烟运动组运动后血浆皮质醇浓度明显高于运动前（P〈0．01），但全部运动结束后次日晨测定的血浆皮质醇浓度与运动前无明显差异（P〉0．05）；③苏木精-伊红染色显示，吸烟组肺组织出现明显的慢性炎症反应，吸烟运动组比吸烟组炎症反应轻。结论适当的良性运动应激能降低由吸烟引起的气道高反应性。     

侧脑室内注射川芎嗪对大鼠肺动脉压的影响

目的 :探讨川芎嗪降低大鼠肺动脉压作用及机制。方法 :以肺动脉压为指标 ,在氨基甲酸乙酯麻醉、三碘季胺酚制动、呼吸机控制呼吸的SD大鼠上观察川芎对大鼠肺动脉压的影响。实验分为五组 ,即川芎嗪组、生理盐水组、心得安 +川芎嗪组、酚妥拉明 +川芎嗪组和阿托品 +川芎嗪组。连续观察 30min肺动脉压曲线变化 ,并与对照组比较。结果 :川芎嗪组给药后大鼠肺动脉压明显降低 ,10～ 15min达最低值 ,与生理盐水组和给药前比较差异显著 (P <0 .0 1)。结论 :川芎嗪有明显降低大鼠肺动脉压作用。侧脑室预先注射β -受体阻断剂心得安可部分阻断川芎嗪的降压效应 ,因此 ,川芎嗪降低肺动脉压的作用可能部分由脑内 β -受体所介导。